Field of the Invention
The embodiments herein generally relate to compounds and methods for releasing H2S in a pH dependent manner. In particular, the invention provides compounds of various formulations which release H2S in a controlled, predictable and sustained manner upon contact with an aqueous environment, such as the circulatory system of an animal, and which are thus suitable for in vivo delivery of H2S.
Discussion of the Related Art
Hydrogen sulfide (H2S) has been recently recognized as a member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide (CO). Studies have demonstrated that the production of endogenous H2S and the exogenous administration of H2S can exert a plurality of protective effects in many pathologies. H2S has also been shown to relax vascular smooth muscle, induce vasodilation of isolated blood vessels, and reduce blood pressure. H2S can also inhibit leukocyte adherence in mesenteric microcirculation during vascular inflammation that further suggests H2S as a potent anti-inflammatory molecule. These results as a whole strongly suggest that modulation of H2S levels has a clear therapeutic value.
Chemical tools that allow precise delivery of H2S are critical for the advancement of research in the field. Traditionally, chemical tools include, sodium sulfide (Na2S) and sodium hydrogen sulfide (NaHS). These salts have the advantage of boosting H2S concentrations rapidly. However, they release H2S spontaneously in aqueous solution, making it hard to control the precise H2S concentration. In addition, H2S concentrations in aqueous solution can rapidly decrease due to volatilization, thus significantly limiting the use of these two H2S sources. As such, there is a need for the development of chemical compounds capable of controllably releasing H2S for use within biological systems.